2. PI3K/Akt/mTOR Autophagy
  3. mTOR Autophagy
  4. OSI-027

OSI-027 (ASP7486) est un inhibiteur de l'activité kinase mTOR qui est puissant, sélectif, oralement actif et ATP-compétitif avec un IC50 de 4 nM. OSI-027 cible mTORC1 et mTORC2 avec des IC50s de 22 nM et 65 nM, respectivement.

OSI-027 (ASP7486) is a potent, selective, orally active and ATP-competitive mTOR kinase activity inhibitor with an IC50 of 4 nM. OSI-027 targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM, respectively.

For research use only. We do not sell to patients.

OSI-027 Chemical Structure

OSI-027 Chemical Structure

CAS No. : 936890-98-1

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 121 In-stock
Solution
10 mM * 1 mL in DMSO USD 121 In-stock
Solid
1 mg USD 44 In-stock
5 mg USD 110 In-stock
10 mg USD 180 In-stock
50 mg USD 560 In-stock
100 mg USD 900 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

Based on 15 publication(s) in Google Scholar

OSI-027 Related Antibodies

Top Publications Citing Use of Products

    OSI-027 purchased from MedChemExpress. Usage Cited in: Oncotarget. 2017 Feb 21;8(8):12775-12783.  [Abstract]

    OSI-027, AZD-8055 and AZD-2014 almost completely block MHY1485-induced mTOR activation (p-mTOR/S6K1/Akt Ser473) in skin keratinocytes.

    OSI-027 purchased from MedChemExpress. Usage Cited in: EBioMedicine. 2015 Nov 19;2(12):1944-56.  [Abstract]

    SW620 xenograft tumors are treated with SB202190 and OSI027 individually or in combination. The effect on signaling by p38 (P-MK2 and P-Hsp27) and mTOR (P-S6K1 and P-AKT) is analyzed by immunoblot. SB202190 achieves on-target inhibition by diminishes phosphorylation of MK2 and Hsp27. OSI-027 blocks signaling by both mTORC1 and mTORC2 by decreases phosphorylation of S6K1 and AKT. When SB202190 and OSI-027 are used in combination, all three kinases, p38, mTORC1 and mTORC2 are potently inhibited.

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    mTOR mTORC1 mTORC2

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    OSI-027 (ASP7486) is a potent, selective, orally active and ATP-competitive mTOR kinase activity inhibitor with an IC50 of 4 nM. OSI-027 targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM, respectively[1][2].

    IC50 & Target[1]

    mTOR

    4 nM (IC50)

    mTORC1

    22 nM (IC50)

    mTORC2

    65 nM (IC50)

    PI3K-γ

    0.42 μM (IC50)

    PI3K-α

    1.3 μM (IC50)

    DNA-PK

    1 μM (IC50)

    Autophagy

     

    In Vitro

    OSI-027 is an ATP-competitive inhibitor, which targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM. OSI-027 also inhibits PI3K-α, PI3K-γ and DNA-PK with IC50s of 1.3 μM, 0.42 μM and 1.0 μM. OSI-027 inhibits mTOR signaling of phospho-4E-BP1 with an IC50 of 1 μM[1].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    OSI-027 Related Antibodies
    In Vivo

    Effects on GEO colorectal xenograft growth treated with Rapamycin or OSI-027 for 12 days are consistent with our in vitro experiments. Treatment with Rapamycin (20 mg/kg) inhibits phospho-S6 and phospho-4E-BP1, while Akt phosphorylation is increased by 29%. In contrast, OSI-027 (65 mg/kg) inhibits both mTORC1 and mTORC2 effectors. After 2 hours, decreased 4E-BP1, Akt, and S6 phosphorylation is observed and inhibition of S6 and Akt is sustained for 24 hours. The plasma drug concentration of OSI-027 inversely correlated with these effects on mTORC1 and mTORC2 signaling. The median plasma drug concentration with OSI-027 is 21.3 μM at 2 hours and 14.9 μM at 8 hours. The in vivo efficacy of OSI-027 plus Sunitinib is tested in H292 human lung and Ovcar-5 human ovarian xenograft tumors. H292 tumors, treated with OSI-027 (50 mg/kg) for 21 days have 61% median tumor growth inhibition for the duration of treatment (TGI). Sunitinib (40 mg/kg) for 21 days had 47% median TGI. Combining OSI-027 with Sunitinib, however, has a median TGI of 100% with 59% maximal tumor regression, a statistically significant improvement over either agent alone. Ovcar-5 xenograft tumors treated with OSI-027 or Sunitinib have a 55% and 68% median TGI, respectively. OSI-027 administered with Sunitinib has a significantly better median TGI of 100% with 38% maximal tumor regression[1].
    In the Rapamycin (RAPA) group, three rats exhibit symptoms typical of LTx-aGVHD and die 27 to 35 days after liver transplantation (LT); the remaining five rats do not develop LTx-aGVHD symptoms and survive for more than 100 days. In contrast, seven rats in the OSI-027 group survive for more than 100 days without symptoms of LTx-aGVHD, and only one rat exhibits LTx-aGVHD symptoms and dies on day 33 after LT[3].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
    Clinical Trial
    Molecular Weight

    406.44

    Formula

    C21H22N6O3
    CAS No.
    Appearance

    Solid

    Color

    Light yellow to yellow

    SMILES

    O=C([C@H]1CC[C@H](C2=NC(C(N3)=CC4=C3C(OC)=CC=C4)=C5C(N)=NC=NN52)CC1)O
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    In solvent -80°C 6 months
    -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (246.04 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.4604 mL 12.3019 mL 24.6039 mL
    5 mM 0.4921 mL 2.4604 mL 4.9208 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

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    Volume (start)

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: 2.5 mg/mL (6.15 mM); Suspended solution; Need ultrasonic

      This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

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    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
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    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.40%

    COA (255 KB) HNMR (210 KB) RP-HPLC (137 KB) LCMS (180 KB)

    Handling Instructions (2659 KB)
    References
    Kinase Assay
    [1]

    Assays of a panel of 40 other recombinant kinases including both protein and lipid kinases are performed at 100 mM ATP concentration by SelectScreen profiling service. A broad panel of kinases is tested at a single concentration of OSI-027 or OXA-01 (3 μM) to evaluate percent inhibition of each kinase or mutant variant, using the Ambit KinomeScan platform[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Cell Assay
    [1]

    To study the effect of drug treatment on cellular signaling, Ovcar-3 cells are plated in normal growth medium. After 24 hours, serum is removed and cells are serum-starved overnight. Rapamycin, OSI-027 and OXA-01 are solubilized in DMSO and added to cells at varying concentrations. After a two-hour incubation cells are growth factor stimulated with 10 ng/mL Insulin for 3 to 5 minutes, then rinsed with cold PBS and lysed[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [1]

    Mice[1]
    For xenograft models, cells are harvested, implanted s.c. in the right flank of nu/nu CD-1 mice and tumor growth is analyzed. Mice bearing GEO xenografts are treated for 12 days with OSI-027 (65mg/kg) or vehicle and tumors collected at 2, 8, and 24 hours. Tumor growth inhibition and regression calculations are included.
    Rats[2]
    Specific pathogen-free female Lewis rats, male BN rats, male Lew-Tg(CAG-EGFP)YsRrrc rats and male Lew-TgYsRrrc rats are used. Orthotopic LT is undertaken. No antibiotics were used. Freshly prepared splenocytes (4×108, suspended in 500 μL PBS) of Lew-Tg YsRrrc rats are infused into each recipient via the dorsal penile vein immediately after LT (within 30 min). LTx-aGVHD model rats are divided into three experimental groups: RAPA (1 mg/kg), OSI-027 (1 mg/kg) or control (equal quantity of vehicle) groups; treatments are administered via the vena caudalis from day 7 to day 15.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 2.4604 mL 12.3019 mL 24.6039 mL 61.5097 mL
    5 mM 0.4921 mL 2.4604 mL 4.9208 mL 12.3019 mL
    10 mM 0.2460 mL 1.2302 mL 2.4604 mL 6.1510 mL
    15 mM 0.1640 mL 0.8201 mL 1.6403 mL 4.1006 mL
    20 mM 0.1230 mL 0.6151 mL 1.2302 mL 3.0755 mL
    25 mM 0.0984 mL 0.4921 mL 0.9842 mL 2.4604 mL
    30 mM 0.0820 mL 0.4101 mL 0.8201 mL 2.0503 mL
    40 mM 0.0615 mL 0.3075 mL 0.6151 mL 1.5377 mL
    50 mM 0.0492 mL 0.2460 mL 0.4921 mL 1.2302 mL
    60 mM 0.0410 mL 0.2050 mL 0.4101 mL 1.0252 mL
    80 mM 0.0308 mL 0.1538 mL 0.3075 mL 0.7689 mL
    100 mM 0.0246 mL 0.1230 mL 0.2460 mL 0.6151 mL
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    OSI-027 Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    OSI-027936890-98-1ASP7486OSI027OSI 027ASP 7486ASP-7486mTORAutophagyMammalian target of RapamycinInhibitorinhibitorinhibit

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